The broad, long-term objectives of this study are to test the effects of different fats on microvascular events as they relate to cardiovascular disease. More directly, we will test fats, rich in specific fatty acid (FA) isomers, in the presence or absence of the antioxidant vitamin E, on 1) capillary blood cell velocity (CBV), 2) blood flow and 3) platelet-endothelial and lipoprotein-endothelial cell interactions. Specific aims are to test the following hypotheses: 1) that isocaloric amounts of fats rich in polyunsaturated FA (n-3, n-6 families) increase CBV, subdermal and total finger blood flow in humans more than saturated or monounsaturated FA, 2) that in humans CBV is incrementally increased by different levels of n-3 and n-6 vs. n-9 FA or a western diet fat blend (WDFB-combination of beef, pork and vegetable fats), 3) that in humans the addition of vitamin E to a fish oil supplement vs. native fish oil will increase CBV, decrease platelet aggregation and protect against lipoprotein induced endothelial cell injury (WDFB will be used as the control), and 4) that fish oil (n-3 rich) vs. olive oil (n-9 rich), safflower oil (n-6 rich) or WDFB fed to mice will decrease in vivo platelet-endothelial cell adherence and platelet aggregation. [This will be tested with and without supplemental vitamin E to test the effects of an antioxidant on highly oxidizable dietary lipids (fish, safflower) vs. a more stable lipid source (olive, WDFB).] To test these hypotheses human subjects and mice will be given fat supplements rich in n-6, n-3, n-9 and saturated fatty acids and measurements at different time intervals made as they relate to the above mentioned cardiovascular parameters. The knowledge gained will enable us to better understand the events contributing to the development of atherosclerosis and thromboembolytic disease.